Conventionally, carbamate- or organophosphorus-based insecticides have been widely used in the relevant field, and these insecticides produce pesticidal effects by inhibiting acetylcholinesterase (AchE). However, the extended use of such insecticides resulted in the development of resistance in the pests, which requires an insecticide having a new mechanism of action, and in response to such need, ryanodine receptors, a class of calcium ion channels have been considered as a new target for pest control.
Due to the fact that homeostasis of calcium particularly plays an important role in muscle contraction, an insecticide that binds to a ryanodine receptor inhibits feeding activities, thereby causing a coma or paralysis, and, ultimately, death in insects.
Examples of commercially available insecticides which bind to ryanodine receptors include: flubendiamide (Phoenix™, Takumi™, EP 1380209 A1, discovered by Nihon Nohyaku, co-developed with Bayer Crop Science); chlorantraniliprole having an anthranilamide structure (Rynaxypyr™, WO 01/070671, developed by DuPont); and cyantraniliprole (Cyazypyr™, WO 04/067528, developed by DuPont).
These compounds induce pesticidal effects by binding to ryanodine receptors to disturb calcium ion channels. It is known that these compounds are particularly effective against moths.
Companies including Bayer, DuPont, Syngenta, Sumitomo, Ishihara Sangyo Kaisha, Nissan, etc. have developed various derivatives of the above compounds, for which about 100 patents were granted. However, only three products, i.e., flubendiamide, chlorantraniliprole and cyantraniliprole, are currently available on the market.
Recently, in the EU, the use of neonicotinoid-based pesticides has been pointed out as one of the reasons that is responsible for the decline of the honeybee population. In January 2013, European Medicines Agency (EMA) published the result of study for issues of neonicotinoid-based pesticides. Based on the findings, the EU Commission suggested banning the use of imidacloprid, clothianidin, thiamethoxam, and decided to vote on banning the use of the products in mid-March of 2013. In Korea, there is a movement led by Rural Development Administration to redress the same issue even before environmental agencies and the National Assembly bring up the issue. As described above, there are concerns not only with the safety of humans, animals and environment in the process of developing insecticides, but with the safety of beneficial insects including honeybee. Under the circumstances, since chlorantraniliprole developed by DuPont exhibits acute contact toxicity of >4 μg/bee (LD50), there is a need for developing an insecticide which is safer for honeybees.
Meanwhile, along with the acute contact toxicity, the half-life of residual insecticides in soil must be also taken into consideration in the process of developing an insecticide. Because the half-life of chlorantraniliprole in soil is approximately 180 days, it will remain in soil for a long time and pose a great risk to the environment. Thus, there is a great need for an environmentally friendly insecticide having a short residual period in soil, which is also safe for honeybees.